Saturday, January 18, 2014

Pfizer Enters a 10K Race Ready for a Marathon

In October 2013, Pfizer (NYSE: PFE ) began a series of Phase 3 studies for bococizumab. The company intends to dose over 22,000 patients in separate trials sorted by risk type and indication. This monoclonal antibody (MAB) is one of an emerging class of therapies that lower cholesterol through inhibition of proprotein convertase subtilisin/kexin type 9, an enzyme mercifully abbreviated to PCSK9.

Why PCSK9 is a target
Low density lipoprotein cholesterol, the "bad" kind that's often referred to as LDL-C, is typically removed from the bloodstream after attaching to LDL receptors on the surface of liver cells. PCSK9's natural function is to regulate the amount of circulating cholesterol by marking LDL receptors for destruction after they carry LDL-C into a liver cell. In theory, any drug that inhibits this enzyme should also lower circulating LDL-C, which in turn should lower a patient's risk of heart attack.

Taking the "mono" out of monoclonal
Pfizer is not alone in the race to develop a monoclonal antibody to inhibit PCSK9. Amgen (NASDAQ: AMGN ) has had some luck with two Phase 3 trials involving its PCSK9 inhibitor, evolocumab. In December 2013, Amgen announced its MAB met its primary endpoint of reducing LDL-C at 52 weeks in a study of 901 hyperlipidemia patients.

This data was no doubt followed by a sigh of relief at Amgen. The study is just one of 13 Phase 3 trials with a combined enrollment of over 28,000 patients.

So far, Amgen has been quiet about the details of the Phase 3 study. Results from several Phase 2 trials have shown it to be roughly as effective as Pfizer's bococizumab, however.

In May 2010, Regeneron Pharmaceuticals (NASDAQ: REGN ) , while partnered with Sanofi (NYSE: SNY ) , was the first team to show that the inhibition of PCSK9 could significantly lower cholesterol levels in humans. In mid-October 2013, the team was also the first to present Phase 3 data showing it to be highly effective with relatively low dosages over a period of 24 weeks. This was just the first of 12 Phase 3 trials with an expected total enrollment of over 23,000 patients.